This invention was made with government support under ER 60502 awarded by the Department of Energy and CA 30688, awarded by the National Cancer Institute. The government has certain rights in the invention.
This invention relates generally to the field of molecular genetics and, more particularly, to methods of detecting proclivity to pathologies resulting from somatic cell mutation.
Mutations are alterations in chemical structure of DNA, the molecule that contains genetic information. While mutations are constantly being introduced into the DNA of dividing cells, cells possess the means, such as DNA repair enzymes, to correct mutations before they are passed on to progeny cells. Nevertheless, the correction mechanism is not perfect and mutations are introduced into mammalian somatic cells at rates of about 10.sup.-7 to about 10.sup.-6 per gene locus per cell generation.
Somatic mutational diseases result from cells bearing a mutation that was inherited or that arose spontaneously and that exists in the progeny of certain somatic cells. One example is cancer.
Many cancer causing agents, such as ultraviolet rays in sunlight and certain chemical compounds, are known to cause genetic mutations. In studying the link between genetic mutations and cancer, scientists identified oncogenes and tumor suppressor genes. When oncogenes are mutated, they can transform a normal cell into a cancer cell. While mutations in oncogenes may not be the only genetic cause of cancer, they do provide a causal link between a genetic event and a disease state.
These facts imply that individuals with faulty DNA repair mechanisms might be more prone to mutations and, therefore, to cancer than normal individuals. This is supported by the discovery of two diseases apparently involving deficiencies in DNA repair mechanisms: xeroderma pigmentosum and ataxia telangiectasia. Individuals with the former disease are subject to a very high incidence of sunlight-induced skin cancer. These individuals are deficient in enzymes repairing the type of damage done to DNA by ultraviolet light. Individuals with the latter disease are subject to an increased risk of breast cancer and appear to have deficiencies in enzymes that influence repair of breaks in the DNA chain.
Thus, there has been a long felt need for methods of identifying individuals who are prone to increased rates of mutation and, therefore, are at higher risk of somatic mutational diseases. Such methods would help doctors prevent such diseases, for example by warning patients to avoid carcinogenic agents, or treat diseases, by alerting doctors to screen for the disease so that it can be found in its early stages, when treatment is likely to be more effective.
There thus exists a need for methods for identifying individuals with a high rate of somatic cell mutation. This invention satisfies this need and provides related advantages as well.